ARCHER Trial Visual Acuity Results in Geographic Atrophy
18 December 2023
Forward-Looking Statements and Disclaimers
This presentation contains "forward-looking" statements about Annexon, Inc. and our industry that involve substantial risks and uncertainties. All statements other than statements of historical facts, including statements regarding topline data from the ARCHER Phase 2 trial and post-hoc analyses, our clinical and preclinical programs, timing and commencement of future nonclinical studies and clinical trials and research and development programs, timing of clinical results, strategic plans for our business and product candidates, including additional indications which we may pursue, our financial position, runway and anticipated milestones, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as "aim," "anticipate," "assume," "believe," "contemplate," "continue," "could," "design," "due," "estimate," "expect," "focus," "goal," "intend," "may," "objective," "plan," "positioned," "potential," "predict," "seek," "should," "target," "will," "would" and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology.
Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, risks and uncertainties related to: the ongoing off-treatmentfollow-up portion of the ARCHER Phase 2 trial and final results from the ARCHER Phase 2 trial; our history of net operating losses; our ability to obtain necessary capital to fund our clinical programs; the early stages of clinical development of our product candidates; the effects of COVID-19 or other public health crises on our clinical programs and business operations; our ability to obtain regulatory approval of and successfully commercialize our product candidates; any undesirable side effects or other properties of our product candidates; our reliance on third-party suppliers and manufacturers; the outcomes of any future collaboration agreements; and our ability to adequately maintain intellectual property rights for our product candidates.
These and other risks are described in greater detail under the section titled "Risk Factors" contained in our Annual Report on Form 10-K and Quarterly Reports on Form 10-Q and our other filings with the Securities Exchange Commission (SEC)Quarterly Report on Form 10-Q filed with the Securities Exchange Commission (SEC) on March 31, 2023 and our other filings with the SEC from time to time. All forward-looking statements in this presentation speak only as of the date of this presentation. Except as required by law, we undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise.
This presentation concerns drug candidates that are under clinical investigation, and which have not yet been approved for marketing by the U.S. Food and Drug Administration (FDA). These are currently limited by federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated.
This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates or statistical data. Neither we nor any other person makes any representation as to the accuracy or completeness of such data or undertakes any obligation to update such data after the date of this presentation.
Comparisons to third-party studies are provided for illustrative purposes only. Differences exist between trial designs, study sites, subject populations and applicable products or candidates, and caution should be exercised when comparing outcomes across studies.
2
2
A bold mission to free
the body, brain and eye from complement-mediated disease
3
Overview of ANX007 Geographic Atrophy Program
Pioneering upstream classical complement trial with demonstrated functional benefit
- Unique MOA targeting classical complement inflammation where it starts
- Preclinical classical complement inhibition protected photoreceptor cell loss and function
- ARCHER 1st clinical demonstration of significant, dose & time-dependent vision preservation
- Vision preservation supported by multiple lines of evidence, including: 12 months on-treatment, fellow- eye, foveal status and off-treatment analyses
- Clinical impact consistently improved over time on BCVA ≥15-letter loss measures
- Generally well tolerated; no CNV increase in treated vs. sham; no reported cases of vasculitis
- ANX007 1st and only EMA PRIME Designation in GA - based on preclinical & ARCHER data set
- Robust global Phase 3 program to confirm ARCHER findings
4
Anti-C1q Mechanism of Action
Classical Complement-Mediated Neurodegeneration Extensively Researched in Ophthalmic and Neurological Diseases
Functional clinical benefit previously demonstrated in Huntington's disease and ALS, and now in GA
Anti-C1q protective in several models, including:
• | Geographic atrophy | |
(photoreceptor damage) | ||
• | Glaucoma | |
• | Retinal ischemia | |
• | Huntington's disease | |
• | Amyotrophic lateral sclerosis | |
Ben Barres, M.D., Ph.D. | • | Alzheimer's disease |
• | Frontotemporal dementia | |
Discoverer of C1q Technology | • | Spinal muscular atrophy |
Scientific Co-Founder, Annexon | • | Traumatic brain injury |
ANTI-C1q PROTECTS AGAINST SYNAPSE LOSS AND
NEURODEGENERATION
- Discovered by Annexon co-founder, Ben Barres, spawning an entire field and validated in multiple labs1
- Synapse loss correlates with functional decline2
- Synapse loss precedes neuronal loss3
6 | 1Stevens, et al., 2007 DOI 10.1016/j.cell.2007.10.036; Schafer et al., 2012 DOI 10.1016/j.neuron.2012.03.026; Hong, et al., 2016 doi: 10.1126/science.aad8373; Lui et al., 2016 doi.org/10.1016/j.cell.2016.04.001; 2Davies et al., 1987 J Neurological Sci |
78:151; Terry, et al., 1991 Ann Neurol 30:572; 3Yoshiyama et al., 2007 DOI 10.1016/j.neuron.2007.01.010 | |
Anti-C1q: A Distinct Neuroprotective Mechanism
C1q initiates classical complement cascade to drive photoreceptor synapse & cell loss and neuroinflammation
• C1q is a key driver of neurodegeneration1 | C1q binds stressed photoreceptor synapses and activates the |
classical pathway |
- C1q anchors classical pathway activation on photoreceptor cells to cause inflammation and loss2
- ANX007 inhibits C1q and all damaging components of the classical pathway3
C1q | Lectin Pathway | |
Alternative Pathway | C4 | C4b |
C4a | ||
C2 | C1q, C4b, C3b: | |
C4a, C3a, C5a: | Tag surface for | |
microglial cell attack | ||
Recruit microglial cells | ||
C3a | C3 | C3b |
C5a C5 C5b-9
C5b-9:
Causes membrane damage
C1q | SYNAPSE | |
C4b | C5b-9 | |
MICROGLIAL CELL | C3b | |
PHOTORECEPTOR CELL
C1q
In GA, C1q also binds photoreceptor cell | RPE CELL |
outer segments, cellular breakdown | |
products and drusen (e.g., CRP, amyloid)4 | DRUSEN |
1Stevens, 2007, Cell 131:1164; Howell, et al., 2011 J Clin Invest. 121:1429; Schafer, et al., 2012 Neuron 74: 691; Stephan et al., 2012 Annu Rev Neurosci 35:369; Hong, et al., 2016 Science. 352:712; Lui, et al., 2016 Cell 165:921; Dejanovic, et al., 2018 Neuron 100:1322; Vukojicic , et al., 2019, Cell Rep. 29:3087; Williams, et al., 2016 Mol Neurodegener 11:26; 2Tassoni, et al., SFN 2022; Annexon data on file; Jiao, et al., 2018 Mol
- Neurodegener 13:45; Katschke, 2018 Sci Rep. 8:7348. 3Lansita, et al., 2017 International Journal of Toxicology, 36:449; 4Yednock, et al., 2022 Int J Retina Vitreous 8:79
Anti-C1q Protected Photoreceptor Cells and Their Function in Models of Photoreceptor Damage
C1q Deposition on Photoreceptor Cells | Anti-C1q Protected Photoreceptors and Function |
and Synapses with Light-Induced Damage | |
3 DAYS POST WHITE | ANTI-C1Q PROTECTED | ||||||
PHOTORECEPTOR CELLS/ | PROTECTED RETINAL | ||||||
CONTROL | LIGHT DAMAGE | ||||||
RETINAL THICKNESS | FUNCTION | ||||||
Photoreceptor | 6 | * | * | ||||
Synapses | C1q localized | ||||||
200 | |||||||
on synapses | ONLinnuclei | a(uV)Amplitude-wave | |||||
photoreceptorofRows | 4 | 150 | |||||
Photoreceptor | 100 | ||||||
2 | |||||||
Cells | |||||||
50 | |||||||
0 | 0 | Anti-C1q | |||||
Control | Anti-C1q | Control |
Annexon data on file | Jiao, et al., 2018 Mol Neurodegener 13(1):45 |
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Photoreceptor Cells, Synapses & Function Lost Prior to RPE in GA
- Photoreceptor cells and their synapses are lost over intact RPE (white box)
- Decreasing gradient of red-labeledsynapses (w/ white arrows) moving toward the lesion on right - loss of synapses is loss of function1
- Also, decreasing gradient of blue-labeledphotoreceptor cells toward lesion - photoreceptors are lost prior to RPE2
- FAF measures RPE loss/lesion growth, but not photoreceptor or synapse loss and correlates poorly w/ visual function3
Photoreceptor cell synapses (OPL)
Photoreceptor cells (ONL)
Intact photoreceptors, synapses | FAF Lesion | |
and RPE furthest from lesion | ||
(no RPE) | ||
OPL | Gradient of synapse loss in OPL above intact RPE nearing lesion edge (on right) | |
Synapses (red dots w/ white arrows) = functional connections1 | ||
ONL |
Retinal Pigmented Epithelium (RPE)
RPE
GA retinal tissue | 200 mm | |
Section Image: Annexon, data on file | Average 12 month | |
GA lesion growth4
Representative FAF image from Fleckenstein et al., 2017, to illustrate position of retinal cross section (yellow bar) relative to lesion
Representative FAF image from Fleckenstein, 2017 showing contextual reference for retinal section (green bar)
1Selkoe, 2002 doi: 10.1126/science.1074069; Burger, et al., doi.org/10.1016/j.ydbio.2021.04.001; 2Bird et al., 2014 JAMA Ophthalmol doi:10.1001/jamaophthalmol.2013.5799; Li, et al., 2018 Retina 38:1937; Pfau, et al.,
- 2020 10.1001/jamaophthalmol.2020.2914; Sarks, et al., 1988 Eye 2:552; 3Heier, et al., 2020 Ophthalmology Retina 4:673; 4Shen, et al., 2020 Ophthalmol Retina 4:899
ARCHER Trial Overview
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Annexon Inc. published this content on 20 December 2023 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 21 December 2023 15:16:35 UTC.